Reviewed, UniProtKB/Swiss-Prot P13498 (CY24A_HUMAN)

Names and origin

Protein names

Recommended name:
    Cytochrome b-245 light chain
Alternative name(s):
    p22 phagocyte B-cytochrome
    Neutrophil cytochrome b 22 kDa polypeptide
    p22-phox
      Short name=p22phox
    Cytochrome b(558) alpha chain
    Cytochrome b558 subunit alpha
    Superoxide-generating NADPH oxidase light chain subunit

Gene names

Name:

CYBA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	195 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide.
Subunit structure	Composed of a heavy chain (beta) and a light chain (alpha). Interacts with DUOX1, DUOX2 and TPO. Interacts with NOX3 and NOX4.
Subcellular location	MembranePotential.
Involvement in disease	Defects in CYBA are a cause of autosomal recessive chronic granulomatous disease (AR-CGD) [MIM:233690]. AR-CGD is characterized by the failure of activated phagocytes to generate superoxide.
Miscellaneous	The heme prosthetic group could be coordinated with residues of the light chain, the heavy chain, or both, and it is possible that more than one heme is present per cytochrome b-245.
Sequence similarities	Belongs to the p22phox family.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Chronic granulomatous disease Disease mutation
Ligand	Heme Iron Metal-binding NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cytochrome complex assembly Inferred from direct assay. Source: UniProtKB electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW hydrogen peroxide biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB inflammatory response Ref.4 Inferred from mutant phenotype. Source: UniProtKB innate immune response Ref.4 Inferred from mutant phenotype. Source: UniProtKB respiratory burst Ref.4 Inferred from mutant phenotype. Source: UniProtKB smooth muscle hypertrophy Inferred from sequence or structural similarity. Source: UniProtKB superoxide release Ref.4 Inferred from mutant phenotype. Source: UniProtKB transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	NADPH oxidase complex Ref.11 Inferred from direct assay. Source: UniProtKB secretory granule Traceable author statement. Source: UniProtKB
Molecular function	SH3 domain binding Inferred from physical interaction. Source: UniProtKB electron carrier activity Ref.4 Traceable author statement. Source: UniProtKB heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW protein heterodimerization activity Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCF1	P14598	4	EBI-986058,EBI-395044

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 195

194

Cytochrome b-245 light chain

PRO_0000144907

Sites

Metal binding

94

1

Iron (heme axial ligand) Potential

Natural variations

Natural variant

24

1

G → R in AR-CGD.

VAR_012755

Natural variant

72

1

H → Y: dbSNP rs4673.

VAR_005122

Natural variant

90

1

R → Q in AR-CGD.

VAR_005123

Natural variant

94

1

H → R in AR-CGD.

VAR_005124

Natural variant

118

1

S → R in AR-CGD.

VAR_005125

Natural variant

156

1

P → Q in AR-CGD.

VAR_005126

Experimental info

Mutagenesis

157

1

P → Q: Loss of interaction with NOXO1

Secondary structure

1

.

.

.

195

Helix Strand Turn

Details...

Helix

161 – 165

5

Sequences

	Sequence		Length	Mass (Da)
	P13498-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 429E97A6A9303510	FASTA	195	20,958
	10 20 30 40 50 60 MGQIEWAMWA NEQALASGLI LITGGIVATA GRFTQWYFGA YSIVAGVFVC LLEYPRGKRK 70 80 90 100 110 120 KGSTMERWGQ KHMTAVVKLF GPFTRNYYVR AVLHLLLSVP AGFLLATILG TACLAIASGI 130 140 150 160 170 180 YLLAAVRGEQ WTPIEPKPRE RPQIGGTIKQ PPSNPPPRPP AEARKKPSEE EAAAAAGGPP 190 GGPQVNPIPV TDEVV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b." Parkos C.A., Dinauer M.C., Walker L.E., Allen R.A., Jesaitis A.J., Orkin S.H. Proc. Natl. Acad. Sci. U.S.A. 85:3319-3323(1988) [PubMed: 3368442] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-26.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TYR-72.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease." Dinauer M.C., Pierce E.A., Bruns G.A.P., Curnutte J.T., Orkin S.H. J. Clin. Invest. 86:1729-1737(1990) [PubMed: 2243141] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-123, VARIANT AR-CGD ARG-118.
[5]	"Characterization of two monoclonal antibodies against cytochrome b558 of human neutrophils." Verhoeven A.J., Bolscher B.G., Meerhof L.J., van Zwieten R., Keijer J., Weening R.S., Roos D. Blood 73:1686-1694(1989) [PubMed: 2469497] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 51-195.
[6]	"Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases." Takeya R., Ueno N., Kami K., Taura M., Kohjima M., Izaki T., Nunoi H., Sumimoto H. J. Biol. Chem. 278:25234-25246(2003) [PubMed: 12716910] [Abstract] Cited for: INTERACTION WITH NOXO1, MUTAGENESIS OF PRO-157.
[7]	"Identification of a novel partner of duox: EFP1, a thioredoxin-related protein." Wang D., De Deken X., Milenkovic M., Song Y., Pirson I., Dumont J.E., Miot F. J. Biol. Chem. 280:3096-3103(2005) [PubMed: 15561711] [Abstract] Cited for: INTERACTION WITH DUOX1; DUOX2 AND TPO.
[8]	"The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators." Ueno N., Takeya R., Miyano K., Kikuchi H., Sumimoto H. J. Biol. Chem. 280:23328-23339(2005) [PubMed: 15824103] [Abstract] Cited for: FUNCTION.
[9]	"Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases." Martyn K.D., Frederick L.M., von Loehneysen K., Dinauer M.C., Knaus U.G. Cell. Signal. 18:69-82(2006) [PubMed: 15927447] [Abstract] Cited for: INTERACTION WITH NOX4.
[10]	"Cytochrome b558-negative, autosomal recessive chronic granulomatous disease: two new mutations in the cytochrome b558 light chain of the NADPH oxidase (p22-phox)." de Boer M., de Klein A., Hossle J.-P., Seger R., Corbeel L., Weening R.S., Roos D. Am. J. Hum. Genet. 51:1127-1135(1992) [PubMed: 1415254] [Abstract] Cited for: VARIANTS AR-CGD GLN-90 AND ARG-94.
[11]	"Point mutation in the cytoplasmic domain of the neutrophil p22-phox cytochrome b subunit is associated with a nonfunctional NADPH oxidase and chronic granulomatous disease." Dinauer M.C., Pierce E.A., Erickson R.W., Muhlebach T.J., Messner H., Orkin S.H., Seger R.A., Curnutte J.T. Proc. Natl. Acad. Sci. U.S.A. 88:11231-11235(1991) [PubMed: 1763037] [Abstract] Cited for: VARIANT AR-CGD GLN-156.
[12]	"156Pro-->Gln substitution in the light chain of cytochrome b558 of the human NADPH oxidase (p22-phox) leads to defective translocation of the cytosolic proteins p47-phox and p67-phox." Leusen J.H., Bolscher B.G., Hilarius P.M., Weening R.S., Kaulfersch W., Seger R.A., Roos D., Verhoeven A.J. J. Exp. Med. 180:2329-2334(1994) [PubMed: 7964505] [Abstract] Cited for: CHARACTERIZATION OF VARIANT AR-CGD GLN-156.
[13]	"Genetic studies of three Japanese patients with p22-phox-deficient chronic granulomatous disease: detection of a possible common mutant CYBA allele in Japan and a genotype-phenotype correlation in these patients." Yamada M., Ariga T., Kawamura N., Ohtsu M., Imajoh-Ohmi S., Ohshika E., Tatsuzawa O., Kobayashi K., Sakiyama Y. Br. J. Haematol. 108:511-517(2000) [PubMed: 10759707] [Abstract] Cited for: VARIANT AR-CGD ARG-24.
+	Additional computationally mapped references.

Web resources

CYBAbase

CYBA mutation db

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBLGenBankDDBJ

M21186 mRNA. Translation: AAA90925.1.
BT006861 mRNA. Translation: AAP35507.1.
BC006465 mRNA. Translation: AAH06465.1.
M62818 , M61106, M62817, M61107 Genomic DNA. Translation: AAA52134.1.

PIR

A28201.

RefSeq

NP_000092.2.

UniGene

Hs.513803

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WLP	NMR	-	A	144-168	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P13498.

Proteomic databases

PeptideAtlas

P13498.

Genome annotation databases

Ensembl

ENSG00000051523. Homo sapiens. [Contig view]

GeneID

1535.

KEGG

hsa:1535.

Organism-specific databases

H-InvDB

HIX0013335.

HGNC

HGNC:2577. CYBA.

HPA

CAB009492.

MIM

233690. phenotype.
608508. gene.

PharmGKB

PA27075.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P13498.

HOVERGEN

P13498.

Gene expression databases

ArrayExpress

P13498.

CleanEx

HS_CYBA.

GermOnline

ENSG00000051523. Homo sapiens.

Family and domain databases

InterPro

IPR007732. Cytochr_b558a.
[Graphical view]

PANTHER

PTHR15168. Cytochr_b558a. 1 hit.

Pfam

PF05038. Cytochrom_B558a. 1 hit.
[Graphical view]

PIRSF

PIRSF019635. Cytochr_b558a. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

6349.

SOURCE

Search...

Entry information

Entry name

CY24A_HUMAN

Accession

Primary (citable) accession number: P13498
Secondary accession number(s): Q14090, Q9BR72

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 23, 2007
Last modified:	November 25, 2008
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)